Dopamine inhibits Na,H-exchanger via D1-like receptor-mediated stimulation of protein kinase A in renal proximal tubules

Dopamine causes natriuresis and diuresis via activation of D-1-like receptors located in the renal proximal tubules. It is reported that this response to dopamine results from the inhibition of Na,H-exchanger and Na,K-ATPase. Earlier studies have suggested a role of protein kinase A (PKA) in the inhibition of Na,H-exchanger, however, the effect of dopamine or the dopamine receptor subtype responsible for the stimulation of PKA has not been reported. Present study was designed to examine the effect of dopamine and D-1-like receptor agonist, SKF 38393, on the stimulation of PKA activity in rat renal proximal tubules. Dopamine and SKF 38393 (1 nM - 1 mu M) caused stimulation of PKA activity, an effect which was antagonized by a D-1-like receptor antagonist, SCH 23390 (10 mu M) Stimulation of PKA activity was also seen with forskolin and di-butyryl cAMP. We also observed that dopamine and SKF 38393 inhibited Na,H-exchanger activity in the proximal tubules. This response was blocked by SCH 23390 and Rp-cAMPS triethylamine, a selective inhibitor of PKA. Similarly, forskolin and di-butyryl cAMP inhibited Na,H-exchanger activity. The data provide direct evidence showing that dopamine, through the activation of D-1-like receptors stimulates PKA activity which in turn inhibits Na,H-exchanger in the proximal tubules.